DNA methylation in pulmonary fibrosis and lung cancer

ABSTRACT

Introduction

Pulmonary fibrosis is an age-related, progressive, and fatal disease with a median survival of 3–5 years after diagnosis; idiopathic pulmonary fibrosis (IPF) is the most common type. It is characterized by fibroblast proliferation and accumulation of excessive extracellular matrix. Patients with IPF are at increased risk for lung cancer. Epigenetic mechanisms are involved in lung fibrosis and cancer, and DNA methylation is critical in disease pathogenesis and progression. Therefore, studies of DNA methylation contribute to better understanding of the underlying mechanisms of these two respiratory diseases, and can offer novel diagnostic and treatment options.

Areas covered

This review discusses the latest advances in our understanding of epigenetic factors related to DNA methylation that impact development of lung cancer and pulmonary fibrosis, discusses the role of DNA methylation in promoting or inhibiting these diseases, and proposes its potential clinical significance in disease diagnosis and treatment.

Expert opinion

DNA methylation plays a critical role in lung cancer and fibrosis pathogenesis. DNA methylation offers a new biomarker for disease diagnosis or monitoring, and provides a new therapeutic target for treatment.

KEYWORDS:

• Biomarkers
• DNA methyl-binding protein
• DNA methylation
• DNA methyltransferases
• epigenetic
• idiopathic pulmonary fibrosis
• lung cancer
• pulmonary fibrosis

Article highlights

• There are many similarities between lung cancer and fibrosis, including the same high-risk factors (old age and smoking), similar pathogenic pathways, and low survival rates.

• Aberrant DNA methylation contributes to both diseases development and progression.

• Increased DNA methyltransferase expression has been reported in lung cancer; however, their roles in IPF remain unclear.

• Methyl-binding proteins are involved in lung cancer and fibrosis pathogenesis.

• DNA hypermethylation silences or downregulates tumor suppressor and/or antifibrotic genes in both diseases. Hypomethylated genes promote lung cancer development, which may not be typical for IPF. However, differentially methylated regions associated with gene expression alterations have been reported in IPF.

• A unique profile of DNA methylation changes occur at early stages in lung cancer or lung fibrosis, allowing DNA methylation to be used as a biomarker for early diagnosis, and to monitor treatment response.

• DNA methylation is a promising therapeutic target for lung cancer and fibrosis treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr. Shan Zhu for editorial assistance.

Author contributions

Conceptualization: X.Z. and Y.Y.S.; draft preparation: J.D., B.Z., Z.F., H. Z., and M.X.; review, editing and revising: X.Z., and Y.Y.S.; funding acquisition: X.Z., J.D., and Y.Y.S. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This work was partially supported by the National Natural Science Foundation of China (No. 81470256) (X.Z.), Natural Science Foundation of Hunan Province, China (No.2020JJ5802) (J.D.), and US NIH grants R01AG050567 and R01HL151702 (Y.Y.S).